The present subject disclosure relates to systems and methods for detecting light for implantable retinal prosthesis.
Degenerative retinal disorders are the leading cause of legal blindness (visually acuity worse than 20/200) in the United States, with age-related macular degermation (AMD) as the main cause among Hispanics and non-Hispanic Whites [1]. 11 million are affected by AMD in the US, with the current numbers projected to reach 22 million by 2050 [2]. About 8 out of 10 people with AMD have the dry form and, over time, patients become functionally blind in both eyes.
Diabetic macular edema (DME) occurs in diabetic patients when high blood sugar levels damage blood vessels which leak into the macula and can lead to permanent vision loss due to the loss of photoreceptors. Cases of DME are estimated to reach 7.8 million in 2020 in the US and Europe [4].
Retinitis pigmentosa (RP) is a rare inherited disease that is estimated to affect 100,000 people in the US [3]. While the numbers of patients affected by RP are much less than those with AMD, it is an even more devastating disorder because the typical age of diagnosis is in the late teens or early twenties. These patients are often completely and profoundly blind by their late thirties or early forties.
Finally, Stargardt disease is a rare inherited form of macular degeneration that causes progressive vision loss in children and young adults. All these forms of degenerative retinal disorders are irreversibly debilitating diseases with a substantial impact on the day-to-day quality of life for individuals as well as their families. Economically, the total amount of support required by RP and Stargardt patients over their lifetimes exceeds those of AMD patients due to age of diagnosis.
Modern implantable retinal prosthetics replace degenerated photoreceptors with optoelectronic hardware. The most common metric for quantifying the loss or restoration of vision is visual acuity (VA), with 20/20 vision accepted as normal and 20/200 as the threshold for blindness. Normal vision corresponds to an angular separation of 1 arcmin or approximately 5 μm on the retina. Correspondingly, a pixel pitch of approximately 50 μm is required for 20/200 vision.
While increasing implant pixel density is necessary to increase visual acuity, it is not sufficient. To replace the function of degenerated photoreceptors [10-15,20], these implants must be able to efficiently convert incident light into electrical current exceeding the neural stimulation threshold, and deliver this stimulating current to activate bipolar cells via the electrode/tissue interface. Applicants and other groups have shown that a stimulating current density of ˜1 mA/mm2 delivered over a 1-4 ms pulse is required to stimulate a retinal bipolar cell in diseased eyes [32]. This current density is several orders of magnitude greater than the photocurrent from photodetectors illuminated by natural light [10].
Several groups (for example, Retina Implant AG and Iridium Medical Technologies) have sought to leverage CMOS (complementary metal-oxide-semiconductor) image sensor technologies in their retinal prosthesis implants [24-29]. Here, each pixel comprises a photodetector and a CMOS circuit consisting of an amplifier to produce and regulate the gain, and an output driver to produce sufficient current to stimulate bipolar neurons. However, the detector, stimulating electrode, and amplifier each occupy significant area and the latter also consumes considerable power and generates heat near sensitive ocular and retinal tissue. This limits the ability to shrink pixel size for higher visual acuity.
On the other hand, retinal prostheses from Pixium Vision and Applicants (Gen1) use cascaded photovoltaic devices and optoelectronic nanowires, respectively, without any amplification but in conjunction with a goggle accessory to produce stimulation. These goggles project pulsed high-irradiance (≥mW/mm2) images of the visual field onto the implanted sensor to produce adequate photocurrent. The projection from the goggles on to the retina through natural eye optics defines the visual field available to the patient. An implanted optoelectronic sensor typically has a smaller FOV (field of view) than the projected image, and the patient can use natural eye scanning motion to observe the visual field. This also allows for natural micro-saccadic movements used by the eye to maintain focus on objects. However, practical power density limits and optical losses in goggle/projector construction along with eye safety limits of long-term NIR exposure [33] constrain the projection FOV and limit the visual experience for the patient. To summarize, any improvements in the efficiency of converting light into stimulating current, will be immediately realized in terms of VA as well as FOV and light exposure safety margin.
What is presented in this subject disclosure is a retinal prosthesis with visual acuity better than 20/150, and higher sensitivity, dynamic range, and FOV than the state-of-the-art. At least two different techniques are presented, the first being an optically-switched vertical single-transistor amplifier for ultrahigh photocurrent amplification, and the second being nanopatterned pillar electrodes.
In one exemplary embodiment, the present subject disclosure is a retinal prosthesis. The prosthesis includes an array of pixels, each pixel containing a photoconductor, a vertical MOSFET amplifier, and a stimulation electrode; and a local return electrode in communication with each pixel to form a local current flow loop between the pixel, a proximal bipolar cell, and the return electrode.
In another exemplary embodiment, the present subject disclosure is a retinal prosthesis. The prosthesis includes an array of pixels, each pixel containing a partially blocked Si/Ge photoconductor, a vertical MOSFET amplifier, and a high CIC IrO stimulation electrode; and a local return electrode in communication with each pixel to form a local current flow loop between the pixel, a proximal bipolar cell, and the return electrode.
In yet another exemplary embodiment, the present subject disclosure is a retinal prosthesis. The prosthesis includes an array of pixels including pillar structure electrodes with nanopatterned stimulation surfaces; and a local return electrode in communication with each pixel to limit electric field spreading and minimize crosstalk.
The present subject disclosure overcomes many of the drawbacks of conventional systems as described above. To develop a retinal prosthesis with visual acuity better than 20/150, and higher sensitivity, dynamic range, and FOV than the state-of-the-art, Applicants propose the following exemplary but non-limiting innovations.
(1) An optically-switched vertical single-transistor amplifier for ultrahigh photocurrent amplification: This design can yield both high sensitivity and packing density. The high sensitivity greatly reduces the required corneal irradiance level so the device could operate with standard intensity AR/VR goggles well within the long-term retinal and corneal safety limits or even under natural light (in bright sunlight), and with a large FOV. The high packing density is enabled by the unique design of the single-transistor vertical amplifier, which (a) reduces the area needed for photodetection due to high responsivity, (b) eliminates area needed for complex amplifier circuitry, and (c) shares the footprint of the stimulating electrode.
(2) Nanopatterned pillar electrodes: In recognition of the high (˜1 mA/mm2) neural stimulation threshold in diseased eyes and the CIC (charge injection capacity) limits of stimulation electrode materials (e.g., IrO), pillar electrodes are proposed here with nanopatterned stimulation surfaces. This will not only increase electrode surface area without increasing footprint, but also bring electrodes closer to the target neurons, minimizing both electrode crosstalk and stimulation threshold. The proposed pixel design also includes local (pixel-wise) return electrodes to limit electric field spreading and further minimize crosstalk.
The innovations in (1) and (2) above significantly advance the field of retinal prostheses by producing a device containing as many as 23,000 pixels at a 35 μm pitch to achieve a VA of 20/150 for a sensor FOV better than 20 degrees and a wide dynamic range. Applicants estimate this optoelectronic hardware would allow the optical power requirement from the goggles to be reduced by at least 2-orders of magnitude compared to current systems. The anticipated performance is a great leap from the state-of-the-art.
Pixel Design
The retinal prosthesis contains a dense array of pixels each comprising a high CIC IrO stimulation electrode atop a vertical single transistor amplifier and a partially-blocked annular amorphous semiconductor photoconductor as a highly photosensitive voltage provider (see
The output current from the vertical transistor flows through an IrO electrode that sits atop the vertical transistor area and occupies the same footprint, in a configuration that produces the most efficient use of the chip real estate. The drain current in the IrO electrode flows into the ionic buffer between the electrode and the retinal bipolar cell as Faradaic current (plus some displacement current as biphasic bias is applied to assure charge balance for each cycle of neural stimulation).
Overall, the high responsivity reduces the required light illumination level by 4 orders of magnitude compared to the cascaded photovoltaic design [12]. Importantly, the single transistor design consumes 1 uW/pixel to achieve neural stimulation, which is more power efficient than CMOS pixels [29]. These features and the efficient use of chip real estate favor high acuity, large FOV (≥20°) retinal prosthesis.
Optically-Controlled, Vertical Single-Transistor Amplifier
A vertical MOSFET follows the typical field-effect-transistor relation in the saturation regime as a planar device:
I
D=(w/2L)μnCi(Vgs−Vth)2
where ID: drain current, W: channel width (the circumference of the device mesa), L: channel length, μn; electron mobility (assuming n-channel FET), Ci: gate capacitance. The gate voltage is controlled by an optically controlled photoconductive switch made of an amorphous Si/Ge thin film with one part of the film exposed to light and another part covered. The resistance of the exposed section and the covered section are modeled by R1 and R2 (
Next to the vertical MOSFET, an a-SiGe or a-Si thin film photoconductor, sensitive to 850 nm wavelength, is deposited on the isolation layer. An a-Si film about 1 μm thick has been previously reported that can vary its own resistance by 3 orders of magnitude from dark to 50 μW/mm2 with visible light [30] owing to its high sensitivity. a-Si and a-SiGe alloys may be used to obtain the photoconductor device with the best sensitivity and controllability of the gate voltage on the vertical MOSFET. The a-Si film has strong sensitivity to green/blue light and its response drops rapidly at red and NIR wavelength. Amorphous SiGe alloys have a much stronger response at red and NIR light and would be particularly suitable for illumination from an NIR goggle. However, high Ge content in the a-SiGe alloy increases the dark current, thus reducing the sensitivity. For the present application, high responsivity to NIR light enhances photosensitivity, and a large photoconductivity change relative to the dark state gives rise to a high voltage swing, thus a high magnitude of transistor switching current. The optimal design for the Ge composition, film thickness, and photoconductor geometry for the exposed and covered sections may be deduced from experimentation.
Penetrating Pillar Electrode and Localized Return Electrode
In the subretinal prosthesis approach, a 30-70 μm thick layer of degenerated photoreceptors separates the implanted electrode array from bipolar cells in the INL of the retina [22,23]. According to one study [35], stimulation current threshold increases roughly proportionally to the square of the separation between the electrode and the targeted cell. Furthermore, the electric field generated by the stimulation spreads through this tissue and may stimulate multiple neurons causing pixel crosstalk and reducing VA. Thus, there are significant advantages to minimizing the distance between stimulating electrode and target neurons. Prior work [22,36] has also shown that when animal retina is placed on surfaces with topology, cells gradually migrate to fill up spaces between positive features. Even when 128 μm tall polymer structures were implanted in Yucatan minipigs, there was no significant gliosis observed or damage to the retina during implantation [22]. Therefore, an optimally designed 3D electrode, that penetrates the retina to deliver stimulation directly to the bipolar cells, and intelligently placed return electrodes to confine the electric field to individual neurons, will complement device-level advances to drive meaningful improvements to VA.
Pillar structures with diameters 12-18 μm and height ranging from 30-70 μm are fabricated on glass or silicon substrates for experimental evaluation in ex vivo animal models. The proposed 3D electrode structures are fabricated using electroplated gold and SIROF.
Experimental Results
Bias Controlled FET Current
The center amplifier is a vertical FET, which can be configured in either a N-P-N or P-N-P configuration for a n-channel or p-channel FET. A dielectric film is deposited on the sidewall of the silicon mesa for passivation and to induce a weak inversion layer along the vertical edge of the middle layer, forming a vertical channel along the mesa sidewall. Silicon dioxide (SiO2) or aluminum oxide (Al2O3) can be used to control the threshold voltage of the sidewall FET.
A layer of metal covers the dielectric layer as the gate terminal to control the channel. The relationship between the current output and the gate voltage can be found in a typical FET equation,
wherein the drain current ID is related to the device height L and the width W of the FET (circumference of the device mesa). VTH is determined by the Si epitaxial layer design and the passivation dielectric layer. ID links with the VGS, the gate voltage that interconnected with the surrounding photoconductor.
In order to adjust the amplification, the FET can also incorporate a third (gate) electrode overlying the thin passivation layer (e.g., SiO2 or Al2O3). The third electrode can be applied as a metal layer overlying the dielectric passivation shown in
Optically Controlled Photoconductive Switch
An amorphous structure is implanted around the amplifier to provide the light sensitive voltage output to the gate of the FET. The principle of the voltage generation from an amorphous structure is demonstrated by the device shown in
Another structure as
This application incorporates by reference herein in their entirety into this disclosure all of the following cited references, which disclose various findings as discussed in the present disclosure:
The foregoing disclosure of the exemplary embodiments of the present subject disclosure has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the subject disclosure to the precise forms disclosed. Many variations and modifications of the embodiments described herein will be apparent to one of ordinary skill in the art in light of the above disclosure. For example, the example measurements and values presented in the disclosure are not limiting of the subject matter, but merely show an example that has been used. It would be apparent to one having ordinary skill in the art that some variation and range is possible and expected with each of the variables presented, and which would result in the desired outcome. The scope of the subject disclosure is to be defined only by the claims appended hereto, and by their equivalents.
Further, in describing representative embodiments of the present subject disclosure, the specification may have presented the method and/or process of the present subject disclosure as a particular sequence of steps. However, to the extent that the method or process does not rely on the particular order of steps set forth herein, the method or process should not be limited to the particular sequence of steps described. As one of ordinary skill in the art would appreciate, other sequences of steps may be possible. Therefore, the particular order of the steps set forth in the specification should not be construed as limitations on the claims. In addition, the claims directed to the method and/or process of the present subject disclosure should not be limited to the performance of their steps in the order written, and one skilled in the art can readily appreciate that the sequences may be varied and still remain within the spirit and scope of the present subject disclosure.
This Patent application claims priority to U.S. Provisional Patent Application Ser. No. 63/197,239, filed Jun. 4, 2021; the content of which is hereby incorporated by reference herein in its entirety into this disclosure.
Number | Date | Country | |
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63197239 | Jun 2021 | US |